Photodegradation products of methylprednisolone suleptanate in aqueous solution--evidence of a bicyclo[3.1.0]hex-3-en-2-one intermediate.
Two major photodegradation products of methylprednisolone suleptanate (sodium 11 beta, 17 alpha-dihydroxy-6 alpha-methyl-21-[[8-[methyl(2-sulfoethyl)amino]-1,8-dioxooctyl+ ++]oxy]-pregna-1,4-diene-3,20-dione) in aqueous solution irradiated with white fluorescent light at 2000 lux for 28 days at 25 degrees C were isolated by preparative high-performance liquid chromatography and characterized. Structures of the photodegradation products were determined as sodium 11 beta,17 alpha-dihydroxy-5 alpha, 6 alpha-dimethyl-21-[[8-[methyl(2-sulfoethyl)amino]-1,8-dioxoocty l]-oxy]-19-norpregna-1(10),3-diene-2,20-dione and sodium 1 beta, 11 beta-epoxy-17 alpha-hydroxy-6 alpha-methyl-21-[[8-[methyl(2-sulfoethyl)amino]-1, 8-dioxooctyl]oxy]-19 alpha-pregn-4-ene-2.20-dione. Formation of these compounds, especially the 1,11-epoxy analogue, strongly supports the existence of the bicyclo[3.1.0]hex-3-en-2-one intermediate in the photorearrangement of steroidal cross-conjugated dienones. The intermediate can account for all the major ketonic and phenolic products; these products are generated from the intermediate after subsequent transformations and/or further skeletal rearrangements. The 1,11-epoxy analogues were obtained from the prednisolone steroids in high yields by irradiation with a high-pressure mercury lamp.
Ogata
M
M
Tsukuba Research Laboratories, Pharmacia & Upjohn Ltd., Ibaraki, Japan.
Noro
Y
Y
Yamada
M
M
Tahara
T
T
Nishimura
T
T
D004355:Drug Stability; D009682:Magnetic Resonance Spectroscopy; D008775:Methylprednisolone / Q000031:analogs & derivatives* / Q000737:chemistry; D010782:Photolysis; D011355:Prodrugs / Q000737:chemistry*; D012996:Solutions; D014867:Water
D011355:Prodrugs; D012996:Solutions; D014867:Water; C052305:methylprednisolone suleptanate; D008775:Methylprednisolone